One-Hour Postoperative Parathyroid Hormone Levels Do Not Reliably Predict Hypocalcemia After Thyroidectomy.

INTRODUCTION: Hypocalcemia is a well-known complication after total thyroidectomy. Studies have indicated that the presence of low postoperative parathyroid hormone (PTH) levels can predict hypocalcemia. However, definitive study designs are lacking. The aim of this study was to determine whether postoperative PTH alone can accurately predict postoperative biochemical hypocalcemia. METHODS: Under IRB approval, a prospective study of 218 consecutive patients who underwent total or completion thyroidectomy by two surgeons between June 2014 and June 2016 was performed. Biochemical hypocalcemia was defined as ionized calcium <1.13 mmol/L or serum calcium <8.4 mg/dL at any time postoperatively. Three PTH thresholds, <10, <20 pg/mL, and >50% drop in PTH 1 h postoperatively from baseline were examined. RESULTS: Postoperative PTH < 10 pg/mL had a sensitivity of 36.5% (95% CI 27.4-46.3%) and a specificity of 89.2% (95% CI 81.9-94.3%). Postoperative PTH < 20 pg/mL had a sensitivity of 66.4% (95% CI 56.6-75.2%) and a specificity of 67.6% (95% CI 58.0-76.2%). Postoperative PTH decrease >50% had a sensitivity of 63.4% (95% CI 53.2-72.7%) and a specificity of 72.5% (95% CI 62.5-81.0%). Across all PTH thresholds, the false-negative rate was 33.6-63.5% indicating that up to 64% of patients with a normal PTH level could have been discharged without appropriate calcium supplementation. The false-positive rate was 10.8-32.4% indicating that up to 32.4% of patients with low PTH could have been treated with calcium supplementation unnecessarily. CONCLUSION: Following total thyroidectomy, PTH levels are unreliable in predicting hypocalcemia. Additional prospective studies are needed to understand the true utility of PTH levels post-thyroidectomy.

Association of Parathyroid Hormone Level With Postthyroidectomy Hypocalcemia: A Systematic Review.

IMPORTANCE: There has been an increased interest in measuring parathyroid hormone (PTH) levels as an early predictive marker for the development of hypocalcemia after total thyroidectomy. However, significant variation exists in the timing, type of assay, and thresholds of PTH in the literature. OBJECTIVE: We performed a systematic review to examine the utility of PTH levels in predicting temporary postthyroidectomy hypocalcemia. EVIDENCE REVIEW: A systematic literature review of studies published prior to May 25, 2016 was performed within PubMed, EMBASE, SCOPUS, and Cochrane databases using the following terms and keywords: "thyroidectomy," "parathyroid hormone," and "hypocalcaemia," "calcium," or "calcitriol." Each candidate full-text publication was reviewed by 2 independent reviewers and selected for data extraction if the study examined the prognostic significance of PTH obtained within 24 hours after thyroidectomy to predict hypocalcaemia. Studies were excluded if calcium supplementation was used routinely or based on a PTH level. Study characteristics, PTH parameters used to predict hypocalcemia, and their respective accuracies were summarized. FINDINGS: The initial search yielded 2417 abstracts. Sixty-nine studies, comprising 9163 patients, were included. Overall, for an absolute PTH threshold, the median accuracy, sensitivity, and specificity were 86%, 85%, and 86%, respectively. For a percentage change over time the median accuracy, sensitivity, and specificity were 89%, 88%, and 90%, respectively. CONCLUSIONS AND RELEVANCE: The existing literature regarding PTH levels to predict postthyroidectomy hypocalcemia is extremely heterogeneous. A single PTH threshold is not a reliable measure of hypocalcemia. Additional prospective studies controlled for timing of laboratory draws and a priori defined PTH thresholds need to be performed to ascertain the true prognostic significance of PTH in predicting postthyroidectomy hypocalcaemia.

Intraoperative PTH May Not Be Necessary in the Management of Primary Hyperparathyroidism Even with Only One Positive or Only Indeterminate Preoperative Localization Studies.

BACKGROUND: Intraoperative PTH (IOPTH) monitoring has been widely used to confirm the removal of the culprit lesion during operation. However, the true benefit of IOPTH in patients with preoperatively well-localized single adenoma has been questioned. The aim of this study was to examine how or if IOPTH changes the surgical management and outcomes in patients with only one positive or only indeterminate localization studies. METHODS: This is a retrospective review of data from a parathyroid surgery database and patient records from July 2004 to June 2014, including patients with primary hyperparathyroidism with a planned MIP by two experienced endocrine surgeons after ≥1 positive/indeterminate preoperative localization study by ultrasound and/or sestamibi. RESULTS: A total of 482 patients with positive (342: 259 only 1, 83 with ≥2) or indeterminate (140: 105 only 1, 35 with ≥2) preoperative imaging studies were included. IOPTH changed the management in only 16 (3%) patients, with an additional lesion found in 12 of them. Surgical cure was achieved in 471 (98%) of patients (98% in the positive vs. 97% in the indeterminate group, p 0.58). With or without IOPTH, the cure rate would not have been significantly different in patients with only 1 positive preoperative imaging (96 vs. 98%, p 0.12). Similar results were seen in those with ≥2 indeterminate (100% cure rate with or without IOPTH). CONCLUSION: Our study suggests that MIP may be safely and successfully performed without IOPTH for patients with ≥1 positive or ≥2 indeterminate preoperative imaging studies. This study is retrospective within inherent biases, and future prospective study is warranted.

Unusual findings in thyroid cytology and histology.

INTRODUCTION: Although cytology and histopathology of thyroid lesions generally fall into common, well-defined categories, there are uncommon cases with unusual fine needle aspiration (FNA) findings or histology. Herein, we review the prevalence and characteristics of rare thyroid cytology and histopathology findings at a tertiary hospital. METHODS: Institutional data from >31,000 patients with a thyroid pathology from 1995 to 2013 were queried. Both cytology and histology were available in 6,693 patients. After exclusion of the common cytological categories detailed by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and common histopathology categories, 90 patients with either an unusual FNA, histopathology, or both were identified. RESULTS: A total of 90 cases were included (19: only unusual FNA; 25: only unusual histology; 46: both unusual cytology and histopathology). The positive predictive value of an unusual FNA for discovering an unusual lesion was 71% (95% CI: 58%-81%). The majority (66%) were females and median age was 59 years. On histopathology, 80 (88%) cases were malignant, 72 (90%) of which were initially diagnosed as malignant on FNA. Of the 10 benign lesions, 8 (80%) also had a benign FNA. Patients with unusual malignant lesions were significantly older than those with unusual benign lesions (62 vs. 44 years; P: 0.004). CONCLUSION: Unusual cytopathological and histopathological findings in thyroid comprise a varied group of tumors that are individually rare but collectively common. A preoperative FNA with an unusual cytopathology is likely to lead to an unusual histopathological diagnosis; however, its diagnostic accuracy in differentiating benign from malignant is lower than the accuracy of cytopathology of conventional TBSRTC. Diagn. Cytopathol. 2017;45:185-190. © 2016 Wiley Periodicals, Inc.

Membrane-type MMPs are indispensable for placental labyrinth formation and development.

The membrane-type matrix metalloproteinases (MT-MMPs) are essential for pericellular matrix remodeling in late stages of development, as well as in growth and tissue homeostasis in postnatal life. Although early morphogenesis is perceived to involve substantial tissue remodeling, the roles of MT-MMPs in these processes are only partially characterized. Here we explore the functions of 2 prominently expressed MT-MMPs, MT1-MMP and MT2-MMP, and describe their roles in the process of placental morphogenesis. The fetal portion of the placenta, in particular the labyrinth (LA), displays strong overlapping expression of MT1-MMP and MT2-MMP, which is critical for syncytiotrophoblast formation and in turn for fetal vessels. Disruption of trophoblast syncytium formation consequently leads to developmental arrest with only a few poorly branched fetal vessels entering the LA causing embryonic death at embryonic day 11.5. Through knockdown of MMP expression, we demonstrate that either MT1-MMP or MT2-MMP is crucial specifically during development of the LA. In contrast, knockdown of MT-MMP activity after LA formation is compatible with development to term and postnatal life. Taken together these data identify essential but interchangeable roles for MT1-MMP or MT2-MMP in placental vasculogenesis and provide the first example of selective temporal and spatial MMP activity required for development of the mouse embryo.

Membrane-type MMPs enable extracellular matrix permissiveness and mesenchymal cell proliferation during embryogenesis.

Peri-cellular remodeling of mesenchymal extracellular matrices is considered a prerequisite for cell proliferation, motility and development. Here we demonstrate that membrane-type 3 MMP, MT3-MMP, is expressed in mesenchymal tissues of the skeleton and in peri-skeletal soft connective tissue. Consistent with this localization, MT3-MMP-deficient mice display growth inhibition tied to a decreased viability of mesenchymal cells in skeletal tissues. We document that MT3-MMP works as a major collagenolytic enzyme, enabling cartilage and bone cells to cleave high-density fibrillar collagen and modulate their resident matrix to make it permissive for proliferation and migration. Collectively, these data uncover a novel extracellular matrix remodeling mechanism required for proper function of mesenchymal cells. The physiological significance of MT3-MMP is highlighted in mice double deficient for MT1-MMP and MT3-MMP. Double deficiency transcends the combined effects of the individual single deficiencies and leads to severe embryonic defects in palatogenesis and bone formation incompatible with life. These defects are directly tied to loss of indispensable collagenolytic activities required in collagen-rich mesenchymal tissues for extracellular matrix remodeling and cell proliferation during embryogenesis.